title: Grb7 and Filamin-a associate and are colocalized to cell membrane ruffles upon EGF stimulation.
abstract: Grb7 is an adaptor molecule mediating signal transduction from multiple cell surface receptors to diverse downstream pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase, ErbB2, are overexpressed in 20-30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, although the participants in these pathways have not been fully determined. In this study, we report the Grb7 protein interacts with Filamin-a, an actin-crosslinking component of the cell cytoskeleton. Additionally, we have demonstrated the interaction between Grb7 and Flna is specific to the RA-PH domains of Grb7, and the immunoglobulin-like repeat 16-19 domains of Flna. We demonstrate that full-length Grb7 and Flna interact in the mammalian cellular environment, as well as in vitro. Immunofluorescent microscopy shows potential co-localization of Grb7 and Flna in membrane ruffles upon epidermal growth factor stimulation. These studies are amongst the first to establish a clear connection between Grb7 signaling and cytoskeletal remodeling.
authors.affiliation: Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, 88003, USA.
authors.forename: Prakash
authors.initials: P
authors.lastname: Paudyal
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shrestha
authors.forename: Thushara
authors.initials: T
authors.lastname: Madanayake
authors.forename: Charles B
authors.initials: CB
authors.lastname: Shuster
authors.forename: Larry R
authors.initials: LR
authors.lastname: Rohrschneider
authors.forename: Aaron
authors.initials: A
authors.lastname: Rowland
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Lyons
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D064448:Filamins / Q000737:chemistry / Q000378:metabolism*; D051382:GRB7 Adaptor Protein / Q000737:chemistry / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects
chemical_list: D064448:Filamins; C495955:GRB7 protein, human; D050505:Mutant Proteins; D051382:GRB7 Adaptor Protein; D014443:Tyrosine; D004815:Epidermal Growth Factor
keywords: ErbB2; Filamin-a; Grb7; HER2; actin binding; cell migration; cytoskeleton; neu